OBJECTIVE: To evaluate the effect of adjunctive risperidone treatment on quality of life in patients with treatment-resistant depression (TRD). METHODS: Data from the open-label treatment phase (4-6 weeks) of an international study designed to evaluate the efficacy, safety, and maintenance effect of risperidone augmentation to SSRI-treatment in TRD. Quality of life was evaluated using the short form of Quality-of-Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q). Change in Q-LES-Q from baseline was analyzed by paired t-test. Correlation analyses between MADRS and Q-LES-Q change scores were performed using Pearson method. RESULTS: This analysis included 386 subjects, mean age 47.1. Baseline and endpoint mean (SD) Q-LES-Q scores were 42.8 (14.6) and 56.0 (18.6), indicating an improvement of 13.2 with risperidone augmentation (P <0.0001). Significant improvements were observed as early as day 7 (P <0.0001). Q-LES-Q item 15, medication satisfaction, was rated as good or very good by 61% of subjects. Correlation between Q-LES-Q and MADRS total change scores at endpoint was -0.6. CONCLUSIONS: These findings suggest that augmentation with risperidone rapidly and significantly improves quality of life in TRD patients. Consistent with previous work, the correlation between Q-LES-Q and MADRS indicate a meaningful relationship between quality of life improvement and symptom relief.